The objectives of this grant proposal involves: 1. Chemical Synthesis of analogs of the naturally occurring sugar phosphates, Alpha-D-ribofuranose-1-phosphate (R-1-P), Alpha-D-2-deoxyribofuranose-1-phosphate (dR-1-P) and 5-0-phosphoryl-Alpha-D-ribofuranose-1-pyrophosphate (PRPP). 2. Examination of analog sugar phosphates as substrates or inhibitors of various enzymes of purine and pyrimidine metabolism: purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase, methylthioadenosine phosphorylase, uridine phosphorylase and thymidine phosphorylase. Examination of effects on enzymes such as phosphoglucomutase, UDPG pyrophosphorylase, and PRPP synthetase. These studies will be performed in collaboration with colleagues in the Roger Williams Cancer Center. 3. Depending on the outcome of the above studies, selected analog sugar phosphates will be reacted with the appropriate enzymes to synthesize novel classes of purine and pyrimidine nucleoside analogs. If analog nucleosides can be prepared in quantities of 20 milligrams or greater, they will be tested for cytotoxicity against a variety of murine and human tumors grown in culture in the Roger Williams Cancer Center.